Genetic Variant CA1:c.-24-1191G>C (chr8-85342850-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001128831.4(CA1):c.-24-1191G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,882 control chromosomes in the GnomAD database, including 21,792 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 21786 hom., cov: 31)

Exomes 𝑓: 0.78 ( 6 hom. )

Consequence

CA1
NM_001128831.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.812

Publications

4 publications found

Variant links:

Genes affected

CA1 (HGNC:1368): (carbonic anhydrase 1) Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. This CA1 gene is closely linked to the CA2 and CA3 genes on chromosome 8. It encodes a cytosolic protein that is found at the highest level in erythrocytes. Allelic variants of this gene have been described in some populations. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Nov 2016]

CA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128831.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CA1	NM_001128831.4	MANE Select	c.-24-1191G>C	intron	N/A	NP_001122303.1
CA1	NM_001128829.4		c.-24-1191G>C	intron	N/A	NP_001122301.1
CA1	NM_001128830.4		c.-101-25G>C	intron	N/A	NP_001122302.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CA1	ENST00000523022.6	TSL:1 MANE Select	c.-24-1191G>C	intron	N/A	ENSP00000429798.1
CA1	ENST00000523953.5	TSL:1	c.-24-1191G>C	intron	N/A	ENSP00000430656.1
CA1	ENST00000431316.3	TSL:5	c.-24-1191G>C	intron	N/A	ENSP00000392338.1

Frequencies

GnomAD3 genomes

AF:

0.529

AC:

80321

AN:

151746

Hom.:

21776

Cov.:

show subpopulations

Gnomad AFR

AF:

0.477

Gnomad AMI

AF:

0.513

Gnomad AMR

AF:

0.503

Gnomad ASJ

AF:

0.547

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.440

Gnomad FIN

AF:

0.676

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.560

GnomAD4 exome

AF:

0.778

AC:

AN:

Hom.:

Cov.:

AF XY:

0.625

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.917

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.700

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.529

AC:

80359

AN:

151864

Hom.:

21786

Cov.:

AF XY:

0.530

AC XY:

39308

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.477

AC:

19743

AN:

41390

American (AMR)

AF:

0.503

AC:

7669

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.547

AC:

1899

AN:

3470

East Asian (EAS)

AF:

0.257

AC:

1326

AN:

5158

South Asian (SAS)

AF:

0.439

AC:

2110

AN:

4808

European-Finnish (FIN)

AF:

0.676

AC:

7124

AN:

10536

Middle Eastern (MID)

AF:

0.541

AC:

159

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38688

AN:

67936

Other (OTH)

AF:

0.558

AC:

1174

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1873

3745

5618

7490

9363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.429

Hom.:

1218

Bravo

AF:

0.518

Asia WGS

AF:

0.354

AC:

1231

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.66

(source)

DANN

Benign

0.66

PhyloP100

-0.81

PromoterAI

0.00020

Neutral

(source)

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over